Olanzapine 2003.

Study characteristics
Methods	Randomisation: randomised, 2:1 ratio, by an interactive voice response system. Allocation: interactive voice response system. Blinding: double‐blind, no further details. Duration: one year, but the study was terminated early. Maximum length was 30 weeks. Design: parallel. Location: multi‐centre. Setting: outpatient.
Participants	Diagnosis: schizophrenia (n = 266) or schizoaffective disorder (n = 60, DSM‐IV). BPRS total score < 36, positive symptoms at most mild, Global Assessment of Functioning at least 40, currently on maintenance antipsychotic medication. N = 326. Gender: 173 men, 153 women. Age: mean 35.9 years. History: duration stable‐ 8 weeks, duration ill‐ mean 11.1 years, number of previous hospitalisations‐ n.i., age at onset‐ mean 24.7 years, severity of illness‐ mean PANSS total score at baseline 43, baseline antipsychotic dose‐ mean 13.4 mg olanzapine/day.
Interventions	Participants were first converted to olanzapine and then stabilised for 8 weeks before randomisation. 1. Drug: olanzapine ‐ Fixed dose of either 10, 15 mg/day or 20 mg/day. Mean dose 13.4 mg/day. N = 224. 2. Placebo: duration of taper: 0 days. N = 102. Rescue medication: a one‐time increase of the same medication (olanzapine or placebo) was allowed. Furthermore, antiparkinson medication and benzodiazepines were allowed.
Outcomes	Examined Relapse: any BPRS positive item > 4, absolute increase of a positive item or of the positive subscore, hospitalisation due to positive symptoms, suicide or suicide attempt. Leaving the study early. Adverse effects. Death, Suicide attempts. Violent/aggressive behaviour Quality of life: Heinrich Carpenter Quality of Life Scale (QLS). Service use ‐ number of participants hospitalised. Unable to use/Not included Mental state: PANSS (no prespecified outcome of interest). Adverse effects: adverse effects with an incidence < 10% (no data), laboratory, EPS‐scales (in part no data/no prespecified outcome of interest), EPS‐scales (no SD/continuous side‐effect results were not among the prespecified outcomes). Physiological measures: vital signs (no prespecified outcome of interest).
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomised, 2:1 ratio, by an interactive voice response system.
Allocation concealment (selection bias)	Low risk	Interactive voice response system.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Double‐blind, no further details.
Blinding (performance bias and detection bias) Subjective outcomes	Unclear risk	Double‐blind, no further details.
Blinding (performance bias and detection bias) Objective outcomes	Low risk	Double‐blind, no further details.
Incomplete outcome data (attrition bias) All outcomes	High risk	The overall attrition of 26% was acceptable, but many more participants in the placebo group than in the olanzapine group left the study early. Kaplan‐Meier survival analysis was used for the analysis of relapse, ANOVA based on LOCF was used for continuous outcomes.
Selective reporting (reporting bias)	High risk	Only those adverse events with a frequency of at least 10% were reported. Use of antiparkinson medication has not been reported.
Other bias	High risk	The study was terminated early when there was a sufficient difference, but this was preplanned.